title: The role of cholinergic anti-inflammatory pathway in acetic acid-induced colonic inflammation in the rat.
abstract: The "cholinergic anti-inflammatory pathway" provides neurological modulation of cytokine synthesis to limit the magnitude of the immune response. This study aimed to evaluate the impact of the cholinergic anti-inflammatory pathway on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid-induced colitis. Colitis was induced by intrarectal administration of 5% acetic acid (1ml) to Sprague-Dawley rats (200-250g; n=7-8 per group). Control group received an equal volume of saline intrarectally. The rats were treated with either nicotine (1mg/kg/day) or huperzine A (0.1mg/kg/day) intraperitoneally for 3 days. After decapitation, the distal colon was scored macroscopically and microscopically. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Formation of reactive oxygen species was monitored by using chemiluminescence (CL). Nuclear factor (NF)-κB expression was evaluated in colonic samples via immunohistochemical analysis. Trunk blood was collected for the assessment of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, resistin and visfatin levels. Both nicotine and huperzine A reduced the extent of colonic lesions, increased colonic MDA level, high MPO activity and NF-κB expression in the colitis group. Elevation of serum IL-1β level due to colitis was also attenuated by both treatments. Additionally, huperzine A was effective to reverse colitis-induced high lucigenin-enhanced CL values and serum TNF-α levels. Colitis group revealed decreased serum visfatin levels compared to control group which was completely reversed by nicotine. In conclusion, modulation of the cholinergic system either by nicotine or ACh esterase inhibition improved acetic acid-induced colonic inflammation as confirmed by macroscopic and microscopic examination and biochemical assays.
authors.affiliation: Marmara University School of Medicine, Department of Physiology, Istanbul, Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Kolgazi
authors.forename: Unal
authors.initials: U
authors.lastname: Uslu
authors.forename: Meral
authors.initials: M
authors.lastname: Yuksel
authors.forename: Ayliz
authors.initials: A
authors.lastname: Velioglu-Ogunc
authors.forename: Feriha
authors.initials: F
authors.lastname: Ercan
authors.forename: Inci
authors.initials: I
authors.lastname: Alican
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003092:Colitis / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000097:blood; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D016207:Cytokines; D016328:NF-kappa B; D018722:Nicotinic Agonists; D052243:Resistin; C499622:Retn protein, rat; D012717:Sesquiterpenes; C050426:huperzine A; D008315:Malondialdehyde; D009538:Nicotine; D009195:Peroxidase; D054409:Nicotinamide Phosphoribosyltransferase; C504970:nicotinamide phosphoribosyltransferase, rat; D005978:Glutathione; D019342:Acetic Acid
keywords: Acetic acid; Cholinergic; Colitis; Huperzine A; Nicotine; Rat